A retrospective study on EU harmonised classifications for carcinogenicity to guide future research

Area of Science:

• Toxicology and chemical risk assessment
• Regulatory science and policy

Background:

• European Regulation (EC) No 1272/2008 (CLP) defines criteria for classifying chemicals as carcinogenic.
• Classifications include Carc. 1A (known human carcinogen), Carc. 1B (presumed), and Carc. 2 (suspected).
• Determining appropriate classification involves evaluating hazard data and human relevance, which can be challenging.

Purpose of the Study:

• To identify and discuss factors influencing the European Chemicals Agency's (ECHA) Committee for Risk Assessment (RAC) decisions on harmonised cancer classifications.
• To prioritize future research on mode of action (MoA) and human relevance in carcinogenicity assessment.

Main Methods:

• Analysis of factors considered by RAC in cancer classification decisions.
• Review of weight-of-evidence (WoE) and strength-of-evidence (SoE) approaches used by RAC.
• Consideration of species-specific tumor data and the relevance of a chemical's MoA to human health.

Main Results:

• RAC's classification decisions are based on a comprehensive WoE and SoE evaluation.
• Key factors include the species exhibiting tumors and the human relevance of the chemical's MoA.
• Understanding MoA is crucial for accurately assessing human carcinogenic risk.

Conclusions:

• The process of harmonised cancer classification under CLP is complex, requiring nuanced scientific judgment.
• Further research into MoA and human relevance is essential for refining carcinogenicity assessments.
• This work provides insights into RAC's decision-making process and highlights areas for future investigation.